CAPON: a protein associated with neuronal nitric oxide synthase that regulates its interactions with PSD95.
Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for N-methyl-D-aspartate (NMDA) receptor-dependent neurotransmitter release, neurotoxicity, and cyclic GMP elevations. The coupling of NMDA receptor-mediated calcium influx and nNOS activation is postulated to be due to a physical coupling of the receptor and the enzyme by an intermediary adaptor protein, PSD95, through a unique PDZ-PDZ domain interaction between PSD95 and nNOS. Here, we report the identification of a novel nNOS-associated protein, CAPON, which is highly enriched in brain and has numerous colocalizations with nNOS. CAPON interacts with the nNOS PDZ domain through its C terminus. CAPON competes with PSD95 for interaction with nNOS, and overexpression of CAPON results in a loss of PSD95/nNOS complexes in transfected cells. CAPON may influence nNOS by regulating its ability to associate with PSD95/NMDA receptor complexes.
Jaffrey
S R
SR
The Johns Hopkins University School of Medicine, Department of Neuroscience, Pharmacology and Molecular Sciences, Baltimore, Maryland 21205, USA.
Snowman
A M
AM
Eliasson
M J
MJ
Cohen
N A
NA
Snyder
S H
SH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003001:Cloning, Molecular; D000076122:Disks Large Homolog 4 Protein; D004347:Drug Interactions; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C488082:NOS1AP protein, rat; D009419:Nerve Tissue Proteins; C110667:Nos1ap protein, mouse; C033652:postsynaptic density proteins; D019001:Nitric Oxide Synthase; D051528:Guanylate Kinases